Transcription outcome of promoters enriched in histone variant H3.3 defined by positioning of H3.3 and local chromatin marks

Biochem Biophys Res Commun. 2015 May 1;460(2):348-53. doi: 10.1016/j.bbrc.2015.03.037. Epub 2015 Mar 14.


Replication-independent histone variant H3.3 is incorporated into distinct genomic regions including promoters. However topology of promoter-associated H3.3 in relation to chromatin modifications and transcriptional outcome is not known, providing no insight on any distinction between H3.3-containing active and inactive promoters. Here, we report algorithms providing information on gene expression status as a function of density and position of multiple chromatin marks on promoters. We identify a relationship between promoter enrichment in epitope-tagged H3.3 or its canonical isoform H3.2 and corresponding transcriptional outcomes, as a function of sub-promoter positioning of DNA methylation and H3K4me3, H3K9me3 and H3K27me3. We identify a low-frequency configuration of H3.3 and H3K9me3 co-occupancy associated with transcriptional activity, while H3.3 and H3K27me3 promoters are invariably inactive. We unveil H3.3 and DNA methylated promoters whose transcription outcome depends on H3.3 sub-promoter positioning. Our results indicate how spatially restricted positioning of H3.3 may add another layer of transcription regulation.

Keywords: Adipose stem cell; Gene expression; H3.3; Histone modification; Promoter.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Chromatin / metabolism*
  • Chromatin Immunoprecipitation
  • DNA Methylation
  • Histones / metabolism*
  • Humans
  • Promoter Regions, Genetic*
  • Transcription, Genetic*


  • Chromatin
  • Histones